GLP-1 RAs Associated With Small ION Risk Increase
Overview
Initiation of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) was linked to a higher adjusted 18-month risk of ischemic optic neuropathy (ION) compared to sodium-glucose cotransporter-2 inhibitors and dipeptidyl peptidase-4 inhibitors in a large observational analysis of commercially insured US adults with type 2 diabetes. The absolute difference in risk was approximately 3 to 4 cases per 10,000 patients.
Background
The association between GLP-1 RAs and ischemic optic neuropathy is due to the increasing use of these medications in managing type 2 diabetes. This study adds to the evidence regarding the safety profile of GLP-1 RAs, particularly concerning ocular health.
Data Highlights
| Medication | ION Risk per 10,000 |
|---|---|
| GLP-1 RA | 9 |
| SGLT2 Inhibitor | 6 |
| DPP-4 Inhibitor | 4 |
Key Findings
- GLP-1 RA initiators had an adjusted cumulative risk of ION of approximately 9 cases per 10,000.
- The risk for SGLT2 inhibitor initiators was about 6 cases per 10,000, resulting in a difference of 3 cases per 10,000.
- Among DPP-4 inhibitor initiators, the risk was approximately 4 cases per 10,000, leading to a difference of about 4 cases per 10,000 compared to GLP-1 RAs.
- 85% of ION events in GLP-1 RA initiators occurred in patients older than 50 years.
- Numerically larger risk differences were observed among patients with preexisting ocular conditions.
- Specific outcome definitions reduced the adjusted risk differences, indicating potential residual confounding.
Clinical Implications
Healthcare providers should be aware of the potential increased risk of ischemic optic neuropathy associated with GLP-1 RA initiation.
Conclusion
This study highlights a potential association between GLP-1 RAs and an increased risk of ischemic optic neuropathy, necessitating further research to clarify these findings and their clinical significance.
Related Resources & Content
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- conexiant, Source, 2025 -- GLP-1 Drugs Linked to GI Effects, Uncertain Signals
- The New Gastroenterologist, Source, 2025 -- GLP-1s Increase GERD Risk Over SGLT2 Inhibitors in T2D
- conexiant, Source, 2025 -- GLP-1 RAs Show Mixed Pancreatitis Risk
- 12. Retinopathy, Neuropathy, and Foot Care: Standards of Care in Diabetes—2026 - PMC, 2026
- GLP-1 Receptor Agonists or SGLT2 Inhibitors and Nonarteritic Anterior Ischemic Optic Neuropathy | Pharmacy and Clinical Pharmacology | JAMA Network Open, 2026
- Semaglutide and the Risk of Nonarteritic Ischemic Optic Neuropathy: A Systematic Review and Certainty of Evidence Meta-Analysis - ScienceDirect, 2026
- 12. Retinopathy, Neuropathy, and Foot Care: Standards of Care in Diabetes—2026 - PMC
- GLP-1 Receptor Agonists or SGLT2 Inhibitors and Nonarteritic Anterior Ischemic Optic Neuropathy | Pharmacy and Clinical Pharmacology | JAMA Network Open | JAMA Network
- Semaglutide and the Risk of Nonarteritic Ischemic Optic Neuropathy: A Systematic Review and Certainty of Evidence Meta-Analysis - ScienceDirect
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